We have initiated a clonal evolution study that enrolls patients with newly diagnosed follicular lymphoma (FL) who have not yet received frontline systemic therapy. The primary objective of this study is to better understand the molecular biology of patients with FL who have an early progression of their disease and/or who are resistant to standard therapy. This prospective study will serially collect human biospecimens including tumor biopsies, bone marrow biopsies, and peripheral blood that will study the clonal evolution of FL patients before they need therapy and until the second time they require systemic therapy. We aim to better define the group of FL patients with high-risk biology in order to preferentially identify novel therapeutic targets in this population. Additionally, the role of circulating tumor DNA In the management of patients with B-cell lymphomas is currently unknown. We published the first paper that identified the role of sequencing-based assays for ctDNA encoding the immunoglobulin receptor prior to disease progression in diffuse large B-cell lymphoma. We have expanded that project across a variety of B-cell lymphomas including mantle cell lymphoma and follicular lymphoma. Further, we collect assays for ctDNA in all of our clinical protocols in order to better define the predictive role of ctDNA to identify early signs of treatment resistance.